The goal of this proposal is to investigate the physiological significance of idiotypic regulation of the immune response. While it is clear that the idiotypic network operates under the conditions of experimental manipulation, evidence for the regulatory significance of the autochthanous anti-idiotope response (driven by the antigen-induced expansion of the idiotope-positive clones) remains elusive. A novel application of the Broome-Gilbert assay for specific translation products is described that makes possible the rapid screening of very large numbers of hybridoma colonies. This technique is demonstrated to be capable of the identification and cloning of extremely rare hybridoma colonies. This procedures will be used to rescue B lymphocytes characteristic of the autochthanous anti-idiotope response with good efficiency even though they are i) infrequent and ii) vastly outnumbered by concurrent idiotope-bearing clones. The monoclonal antibodies secreted by the isolated hybridoma lines will be used in physiologic amounts as immunoregulatory agents. The physical and immunobiological nature of these antibodies will be determined and compared to already existing heterologous and isologous monoclonal anti-idiotope antibodies.